Evans Jennifer R, Michelessi Manuele, Virgili Gianni
Cochrane Eyes and Vision Group, ICEH, London School of Hygiene & Tropical Medicine, Keppel Street, London, UK, WC1E 7HT.
Cochrane Database Syst Rev. 2014 Nov 24;2014(11):CD011234. doi: 10.1002/14651858.CD011234.pub2.
Diabetic retinopathy is a complication of diabetes in which high blood sugar levels damage the blood vessels in the retina. Sometimes new blood vessels grow in the retina, and these can have harmful effects; this is known as proliferative diabetic retinopathy. Laser photocoagulation is an intervention that is commonly used to treat diabetic retinopathy, in which light energy is applied to the retina with the aim of stopping the growth and development of new blood vessels, and thereby preserving vision.
To assess the effects of laser photocoagulation for diabetic retinopathy compared to no treatment or deferred treatment.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 June 2014.
We included randomised controlled trials (RCTs) where people (or eyes) with diabetic retinopathy were randomly allocated to laser photocoagulation or no treatment or deferred treatment. We excluded trials of lasers that are no longer in routine use. Our primary outcome was the proportion of people who lost 15 or more letters (3 lines) of best-corrected visual acuity (BCVA) as measured on a logMAR chart at 12 months. We also looked at longer-term follow-up of the primary outcome at two to five years. Secondary outcomes included mean best corrected distance visual acuity, severe visual loss, mean near visual acuity, progression of diabetic retinopathy, quality of life, pain, loss of driving licence, vitreous haemorrhage and retinal detachment.
We used standard methods as expected by the Cochrane Collaboration. Two review authors selected studies and extracted data.
We identified a large number of trials of laser photocoagulation of diabetic retinopathy (n = 83) but only five of these studies were eligible for inclusion in the review, i.e. they compared laser photocoagulation with currently available lasers to no (or deferred) treatment. Three studies were conducted in the USA, one study in the UK and one study in Japan. A total of 4786 people (9503 eyes) were included in these studies. The majority of participants in four of these trials were people with proliferative diabetic retinopathy; one trial recruited mainly people with non-proliferative retinopathy. Four of the studies evaluated panretinal photocoagulation with argon laser and one study investigated selective photocoagulation of non-perfusion areas. Three studies compared laser treatment to no treatment and two studies compared laser treatment to deferred laser treatment. All studies were at risk of performance bias because the treatment and control were different and no study attempted to produce a sham treatment. Three studies were considered to be at risk of attrition bias.At 12 months there was little difference between eyes that received laser photocoagulation and those allocated to no treatment (or deferred treatment), in terms of loss of 15 or more letters of visual acuity (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.89 to 1.11; 8926 eyes; 2 RCTs, low quality evidence). Longer term follow-up did not show a consistent pattern, but one study found a 20% reduction in risk of loss of 15 or more letters of visual acuity at five years with laser treatment. Treatment with laser reduced the risk of severe visual loss by over 50% at 12 months (RR 0.46, 95% CI 0.24 to 0.86; 9276 eyes; 4 RCTs, moderate quality evidence). There was a beneficial effect on progression of diabetic retinopathy with treated eyes experiencing a 50% reduction in risk of progression of diabetic retinopathy (RR 0.49, 95% CI 0.37 to 0.64; 8331 eyes; 4 RCTs, low quality evidence) and a similar reduction in risk of vitreous haemorrhage (RR 0.56, 95% CI 0.37 to 0.85; 224 eyes; 2 RCTs, low quality evidence).None of the studies reported near visual acuity or patient-relevant outcomes such as quality of life, pain, loss of driving licence or adverse effects such as retinal detachment.We did not plan any subgroup analyses, but there was a difference in baseline risk in participants with non-proliferative retinopathy compared to those with proliferative retinopathy. With the small number of included studies we could not do a formal subgroup analysis comparing effect in proliferative and non-proliferative retinopathy.
AUTHORS' CONCLUSIONS: This review provides evidence that laser photocoagulation is beneficial in treating proliferative diabetic retinopathy. We judged the evidence to be moderate or low, depending on the outcome. This is partly related to reporting of trials conducted many years ago, after which panretinal photocoagulation has become the mainstay of treatment of proliferative diabetic retinopathy.Future Cochrane Reviews on variations in the laser treatment protocol are planned. Future research on laser photocoagulation should investigate the combination of laser photocoagulation with newer treatments such as anti-vascular endothelial growth factors (anti-VEGFs).
糖尿病视网膜病变是糖尿病的一种并发症，高血糖水平会损害视网膜中的血管。有时视网膜会生长出新的血管，这些血管可能会产生有害影响；这被称为增殖性糖尿病视网膜病变。激光光凝是一种常用于治疗糖尿病视网膜病变的干预措施，其通过向视网膜施加光能，以阻止新血管的生长和发育，从而保护视力。
评估与不治疗或延迟治疗相比，激光光凝治疗糖尿病视网膜病变的效果。
我们检索了Cochrane中心对照试验注册库（CENTRAL）（其中包含Cochrane眼科和视力组试验注册库）（2014年第5期）、Ovid MEDLINE、Ovid MEDLINE 正在进行及其他未索引的引用文献、Ovid MEDLINE每日更新版、Ovid OLDMEDLINE（1946年1月至2014年6月）、EMBASE（1980年1月至2014年6月）、对照试验元注册库（mRCT）（www.controlled-trials.com）、ClinicalTrials.gov（www.clinicaltrials.gov）以及世界卫生组织（WHO）国际临床试验注册平台（ICTRP）（www.who.int/ictrp/search/en）。我们在电子检索试验时未设置任何日期或语言限制。我们最后一次检索电子数据库的时间是2014年6月3日。
我们纳入了随机对照试验（RCT），其中患有糖尿病视网膜病变的人（或眼睛）被随机分配接受激光光凝治疗或不治疗或延迟治疗。我们排除了不再常规使用的激光试验。我们的主要结局是在12个月时，使用对数最小分辨角视力（logMAR）图表测量，最佳矫正视力（BCVA）丧失15个或更多字母（3行）的人群比例。我们还观察了主要结局在两到五年的长期随访情况。次要结局包括平均最佳矫正远视力、严重视力丧失、平均近视力、糖尿病视网膜病变的进展、生活质量、疼痛、驾照丧失、玻璃体积血和视网膜脱离。
我们采用了Cochrane协作网预期的标准方法。两位综述作者选择研究并提取数据。
我们识别出大量关于糖尿病视网膜病变激光光凝治疗的试验（n = 83），但其中只有五项研究符合纳入本综述的条件，即它们将激光光凝治疗与目前可用的激光治疗与不治疗（或延迟治疗）进行了比较。三项研究在美国进行，一项研究在英国进行，一项研究在日本进行。这些研究共纳入了4786人（9503只眼睛）。其中四项试验中的大多数参与者为增殖性糖尿病视网膜病变患者；一项试验主要招募非增殖性视网膜病变患者。四项研究评估了氩激光全视网膜光凝，一项研究调查了非灌注区的选择性光凝。三项研究将激光治疗与不治疗进行了比较，两项研究将激光治疗与延迟激光治疗进行了比较。所有研究均存在实施偏倚风险，因为治疗组和对照组不同，且没有研究尝试进行假治疗。三项研究被认为存在失访偏倚风险。在12个月时，接受激光光凝治疗的眼睛与分配至不治疗（或延迟治疗）的眼睛相比，在视力丧失15个或更多字母方面差异不大（风险比（RR）0.99，95%置信区间（CI）0.89至1.11；8926只眼睛；2项RCT，低质量证据）。长期随访未显示出一致的模式，但一项研究发现，激光治疗在五年时使视力丧失15个或更多字母的风险降低了20%。激光治疗在12个月时将严重视力丧失的风险降低了50%以上（RR 0.46，95%CI 0.24至0.86；9276只眼睛；4项RCT，中等质量证据）。对糖尿病视网膜病变的进展有有益影响，接受治疗的眼睛糖尿病视网膜病变进展风险降低了50%（RR 0.49，95%CI 0.37至0.64；8331只眼睛；4项RCT，低质量证据），玻璃体积血风险也有类似程度的降低（RR 0.56，95%CI 0.37至0.85；224只眼睛；2项RCT，低质量证据）。没有研究报告近视力或与患者相关的结局，如生活质量、疼痛、驾照丧失或视网膜脱离等不良反应。我们未计划进行任何亚组分析，但与增殖性视网膜病变患者相比，非增殖性视网膜病变参与者的基线风险存在差异。由于纳入研究数量较少，我们无法进行正式的亚组分析来比较增殖性和非增殖性视网膜病变的治疗效果。
本综述提供的证据表明，激光光凝治疗增殖性糖尿病视网膜病变有益。根据结局不同，我们判断证据质量为中等或低等。这部分与多年前进行的试验报告有关，此后全视网膜光凝已成为增殖性糖尿病视网膜病变治疗的主要方法。计划未来进行关于激光治疗方案差异的Cochrane综述。未来关于激光光凝的研究应探讨激光光凝与抗血管内皮生长因子（anti-VEGFs）等新治疗方法的联合应用。
